The goal of this project is to develop a novel traceless linker for use in combinatorial chemistry. Afer establishing some basic chemistry including the synthesis of cephalosporolide D, we will seek to synthesize a small library of peptidomimetic inhibitors that will be screened against a variety of enzyme targets, such as ras-farnesyl transferase (involved in cancer), cathepsin D (tumor metastasis), angiotensin converting enzyme (hypertension), neutral endopeptidase (congestive heart failure) and thrombin (hemostasis and blood clotting). The key event in the synthesis will be a radical ring-expansion reaction on solid support that simultaneously releases the desired inhibitors from the resin. Radical reactions have emerged as powerful options in solution-phase chemistry, but comparatively little is known about radical reactions on solid support. Our project will provide useful insights in this area. Fortunately, possible side reactions in the radical cleavage step should not compromise the purity of the desired inhibitors, thus guaranteeing meaningful results in the biological screening.